The DNA cleavage mechanism of iron-bleomycin. Kinetic resolution of strand scission from base propenal release

The action of iron-bleomycin and O₂ in cleaving DNA has been resolved into two kinetic events following the initial attack on DNA by the kinetically competent drug species, 'activated bleomycin'. At 4°C, DNA strand scission, monitored both viscometrically and fluorimetrically (T( 1/2 ) = 2.5-5 min), precedes the release from DNA of nucleic base propenals, which is half complete in about 40 min. Therefore, a moderately stable intermediate consisting of cleaved DNA bearing a base propenal precursor is formed. The release of tritium from deoxyribose carbon-2 occurs at the time of DNA scission, which is consistent with the base propenal precursor retaining the deoxyribose-3'-phosphate bond. Specific mechanistic proposals are discussed.